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Regulation of the Orphan Nuclear Receptor Nr2f2 by the DFNA15 Deafness Gene Pou4f3.

Tornari, C; Towers, ER; Gale, JE; Dawson, SJ; (2014) Regulation of the Orphan Nuclear Receptor Nr2f2 by the DFNA15 Deafness Gene Pou4f3. PLoS One , 9 (11) , Article e112247 . 10.1371/journal.pone.0112247. Green open access

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Abstract

Hair cells are the mechanotransducing cells of the inner ear that are essential for hearing and balance. POU4F3 - a POU-domain transcription factor selectively expressed by these cells - has been shown to be essential for hair cell differentiation and survival in mice and its mutation in humans underlies late-onset progressive hearing loss (DFNA15). The downstream targets of POU4F3 are required for hair cell differentiation and survival. We aimed to identify such targets in order to elucidate the molecular pathways involved in hair cell production and maintenance. The orphan thyroid nuclear receptor Nr2f2 was identified as a POU4F3 target using a subtractive hybridization strategy and EMSA analysis showed that POU4F3 binds to two sites in the Nr2f2 5' flanking region. These sites were shown to be required for POU4F3 activation as their mutation leads to a reduction in the response of an Nr2f2 5' flanking region reporter construct to POU4F3. Immunocytochemistry was carried out in the developing and adult inner ear in order to investigate the relevance of this interaction in hearing. NR2F2 expression in the postnatal mouse organ of Corti was shown to be detectable in all sensory epithelia examined and characterised. These data demonstrate that Nr2f2 is a direct target of POU4F3 in vitro and that this regulatory relationship may be relevant to hair cell development and survival.

Type: Article
Title: Regulation of the Orphan Nuclear Receptor Nr2f2 by the DFNA15 Deafness Gene Pou4f3.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0112247
Publisher version: http://dx.doi.org/10.1371/journal.pone.0112247
Language: English
Additional information: PMCID: PMC4221282 © 2014 Tornari et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
URI: https://discovery.ucl.ac.uk/id/eprint/1456253
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